Treating refractory chronic graft-versus-host disease with extracorporeal photochemotherapy.

Extracorporeal photochemotherapy (ECP; photopheresis), an immunomodulatory therapy, has previously demonstrated promising results in treating chronic graft-versus-host disease (cGvHD). We treated six patients (ages 33-54 years) with long-standing refractory extensive-stage cGvHD. ECP was performed thrice weekly initially in all patients. Concomitant therapies included prednisone (n=6), tacrolimus (n=5), cyclosporin A (n=2), hydroxychloroquine (n=2), mycophenolate mofetil (n=1), and psoralen plus ultraviolet A radiation (n=1). After an average of 7.2 months (range, 2-13 months) of ECP, all patients experienced either improvement or stabilization in sclerodermatous skin changes, as well as partial improvements in liver enzyme levels. Skin softening occurred in four patients and was noted as early as 3-8 weeks into treatment. Two patients were able to taper steroid therapy, and two patients were able to taper ECP to twice weekly. ECP was well tolerated. Our results support those of previous studies, suggesting that ECP may be beneficial in patients with refractory cGvHD.

Dose-response effect of combination hydrocodone with ibuprofen in patients with moderate to severe postoperative pain.

OBJECTIVE: The objective of this study was to demonstrate a dose-response effect with 1- and 2-tablet doses of combination hydrocodone 7.5 mg with ibuprofen 200 mg and placebo in patients with moderate to severe postoperative abdominal or gynecologic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. Previous studies with this combination have demonstrated that the components have an additive analgesic effect as well as efficacy compared with other fixed-dose combination analgesics. METHODS: This randomized, parallel-group, double-blind, single-dose, placebo-controlled study compared 1 tablet of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), 2 tablets of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), and placebo (n = 60) in patients with moderate or severe pain after abdominal or gynecologic surgery. Analgesia was evaluated over 8 hours. RESULTS: Mean pain relief (PR) scores were significantly greater for the 2-tablet dose than for the 1-tablet dose at 80 (P = 0.027) and 100 (P = 0.017) minutes and at 2 (P = 0.013), 2.5 (P = 0.012), 3 (P = 0.006), 4 (P = 0.029), 5 (P = 0.002), 6 (P = 0.032), 7 (P = 0.036), and 8 (P = 0.01) hours. Mean pain intensity difference scores were significantly greater for the 2-tablet dose than for the 1-tablet dose at 80 (P = 0.013) and 100 (P = 0.007) minutes and at 2 (P = 0.003), 2.5 (P = 0.002), 3 (P = 0.002), 4 (P = 0.009), 5 (P < 0.001), 6 (P = 0.004), 7 (P = 0.009), and 8 (P = 0.001) hours. Mean total PR scores were significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.01; 0 to 4 hours, P = 0.006; 0 to 6 hours, P = 0.003; 0 to 8 hours, P = 0.003). Mean sum of pain intensity differences was significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.004; 0 to 4 hours, P < 0.001; 0 to 6 hours, P < 0.001; 0 to 8 hours, P < 0.001). Mean peak PR score and median time-to-remedication were significantly greater for the 2-tablet dose than for the 1-tablet dose (P < 0.029 and P = 0.017, respectively). Both doses were superior to placebo. There were no significant differences in the number of patients experiencing adverse events between the 2-tablet dose (n = 6 [10.0%]), the 1-tablet dose (n = 4 [6.7%]), and placebo (n = 1 11.7%]). Adverse events were not serious, and none of the patients discontinued therapy because of side effects. CONCLUSIONS: This study demonstrated that a 2-tablet dose of hydrocodone with ibuprofen provided significantly more analgesia than a 1-tablet dose (a positive dose-response effect) and that both doses were superior to placebo.

Combination hydrocodone and ibuprofen versus combination codeine and acetaminophen for the treatment of chronic pain.

OBJECTIVE: The objective of this study was to compare the effectiveness of combination hydrocodone 7.5 mg and ibuprofen 200 mg with that of combination codeine 30 mg and acetaminophen 300 mg for the treatment of chronic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. METHODS: In this randomized, parallel-group, double-blind, repeated-dose, active-comparator, 4-week, multicenter study, 469 patients were randomly assigned to receive a 1-tablet (n = 156) or 2-tablet (n = 153) dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg (HI1 and HI2, respectively) or a 2-tablet dose of combination codeine 30 mg and acetaminophen 300 mg (CA, n = 160), the active comparator, every 6 to 8 hours as needed for pain. Efficacy was measured through pain relief scores, number of daily doses of study medication, number of daily doses of supplemental analgesics, number of patients who discontinued therapy due to an unsatisfactory analgesic response, and global assessment scores. RESULTS: Of the 469 patients, 255 (54.4%) were female and 214 (45.6%) were male. The mean age was 51.1 years. Types of chronic pain included back (214; 45.6%), arthritic (145; 30.9%), other musculoskeletal (65; 13.9%), cancer (6; 1.3%), diabetic neuropathic (3; 0.6%), postherpetic neuralgic (5; 1.1%), other neurologic (21; 4.5%), and other unclassified chronic pain (10; 2.1%). During the 48 hours prior to the study, 351 (74.8%) patients had been treated with opioid or opioid-nonopioid combination analgesics. The overall mean daily pain relief score was significantly greater in the HI2 group (2.25+/-0.89) than in the HI1 group (1.98+/-0.87) (P = 0.003) or the CA group (1.85+/-0.96) (P < 0.001). The overall mean number of daily doses of study medication was significantly less in the HI2 group (2.94+/-0.99) than in the HI1 group (3.23+/-0.76) (P = 0.036) or the CA group (3.26+/-0.75) (P = 0.014). The overall mean number of daily doses of supplemental analgesics was significantly less in the HI2 group (0.24+/-0.49) than in the HI1 group (0.34+/-0.58) (P = 0.021) or CA group (0.49+/-0.85) (P = 0.010). The number of patients who discontinued treatment due to an unsatisfactory analgesic response was significantly less in the HI2 group (2; 1.3%) than in the CA group (12; 7.5%) (P = 0.008). HI2 was more effective than HI1 and CA as measured by pain relief scores for week 1 (P < 0.001 vs HI1 and CA), week 2 (P < 0.001 vs HI1 and CA), and week 3 (P = 0.008 vs HI1 and P < 0.001 vs CA); daily doses of study medication for week 1 (P = 0.019 vs HI1 and P = 0.011 vs CA); daily doses of supplemental analgesics for week 1 (P = 0.010 vs HI1 and CA); and global assessment scores for week 1 (P = 0.018 vs HI1 and P < 0.001 vs CA), week 2 (P = 0.005 vs HI1 and P < 0.001 vs CA), and week 4 (P = 0.013 vs HI1 and P = 0.023 vs CA). There were no significant differences between HI1 and CA in any efficacy variable. There were no significant differences in the number of patients experiencing adverse events in the HI2 (127; 83%), HI1 (124; 79.5%), and CA (129; 80.6%) groups. However, the mean number of patients who discontinued treatment due to adverse events was significantly greater in the HI2 group (40; 26.1%) than in the HI1 group (23; 14.7%) (P = 0.013). CONCLUSIONS: The results of this study suggest that 2-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be more effective than either 1-tablet doses of this combination or 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg. Moreover, 1-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be as effective as 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg.

Extracorporeal photochemotherapy alone or with adjuvant therapy in the treatment of cutaneous T-cell lymphoma: a 9-year retrospective study at a single institution.

BACKGROUND: Extracorporeal photochemotherapy (ECP; photopheresis) is a treatment option for cutaneous T-cell lymphoma (CTCL). OBJECTIVE: This study describes the outcomes obtained with ECP alone or with adjuvant therapy in treating CTCL. METHODS: A 9-year retrospective study was performed at a single institution. RESULTS: Among 69 patients, 37 were treated with 6 months or more of ECP alone over an average of 36.9 months. Of these patients, 68% (25/37) had stage T2, 5% (2/37) had stage T3, and 27% (10/37) had stage T4 CTCL. Complete response (no skin or systemic disease for 1 month or more) and partial response (50%-99% skin improvement for 1 month or more) were achieved by 14% (5/37) and 41% (15/37) of patients, respectively, giving an overall response rate of 54% (20/37). In recalcitrant patients, adjuvant therapy significantly increased the response rate from 31% (4/13) to 69% (9/13) (P = 0.004). ECP was well tolerated in the entire patient population. CONCLUSION: Response rates in this study compared favorably with those in previous studies, underscoring the potential value of ECP in treating CTCL. To our knowledge, this investigation included the largest group of CTCL patients ever treated with ECP at a single institution.

Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of postoperative obstetric or gynecologic pain.

OBJECTIVE: The objective of this study was to compare the effectiveness of combination hydrocodone and ibuprofen with that of combination oxycodone and acetaminophen in the treatment of moderate to severe postoperative obstetric or gynecologic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. METHODS: This randomized, double-blind, parallel-group, single-dose, active-comparator, placebo-controlled study compared the effects of a 2-tablet dose of hydrocodone 7.5 mg and ibuprofen 200 mg with those of a 2-tablet dose of oxycodone 5 mg and acetaminophen 325 mg and placebo. Analgesia was assessed over 8 hours. RESULTS: Mean pain relief (PR) scores were similar for the hydrocodone with ibuprofen and oxycodone with acetaminophen groups (n = 61 and 59, respectively) at 0.5, 1, 1.5, 2, 2.5, 3, 4, and 7 hours and significantly greater for the hydrocodone with ibuprofen group at 5, 6, and 8 hours (P < or = 0.05). Mean pain intensity difference (PID) scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen at 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours and significantly greater for hydrocodone with ibuprofen at 5, 6, 7, and 8 hours (P < or = 0.05). Total PR scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3- and 0- to 4-hour intervals and significantly greater for hydrocodone with ibuprofen for the 0- to 6- and 0- to 8-hour intervals (P < 0.05). The sum of the PID scores was similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3-, 0- to 4-, 0- to 6-, and 0- to 8-hour intervals. The median estimated time to onset of analgesia, mean peak PR score, median time to remedication, and mean global assessment score were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen. Assay sensitivity was demonstrated by the presence of statistically significant differences between both active treatments and placebo (n = 60). The number of patients experiencing adverse events was similar for each of the 3 groups (11 [18.0%], hydrocodone with ibuprofen; 7 [11.9%], oxycodone with acetaminophen; and 6 [10.0%], placebo). CONCLUSIONS: In this study, a 2-tablet dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg was as effective as a 2-tablet dose of combination oxycodone 5 mg and acetaminophen 325 mg in the treatment of moderate to severe postoperative obstetric or gynecologic pain. Both treatments were superior to placebo. The results of this study suggest that the combination of hydrocodone 7.5 mg and ibuprofen 200 mg may offer prescribers an additional option in combination pain therapy.

Scleromyxedema with dermato-neuro syndrome.

Scleromyxedema is a rare connective tissue disease of unknown cause characterized by a generalized papular eruption, dermal fibroblast proliferation, and monoclonal paraproteinemia. A paroxysmal triad consisting of high fever, seizures, and coma with a flu-like prodrome can rarely occur in patients with scleromyxedema and is termed "dermato-neuro syndrome." We describe a 41-year-old patient with scleromyxedema in whom the dermato-neuro syndrome developed.

Extracorporeal photochemotherapy in progressive systemic sclerosis: a follow-up study.

BACKGROUND: Extracorporeal photochemotherapy (photopheresis), an immune-modulating therapy, has been demonstrated to elicit a therapeutic response in the treatment of several autoimmune disorders. We evaluated the use of photopheresis in the treatment of patients with progressive systemic sclerosis (PSS; scleroderma). METHODS: Five patients with early-onset, diffuse PSS were treated with photopheresis on 2 successive days monthly for an average of 59 months (range 54-89 months). We initially reported the response this group of patients had to photopheresis treatment at an average of 11 months (range 6-21 months). RESULTS: An improvement or stabilization was noted in most patients in skin thickening, joint mobility, pulmonary function studies, oral aperture, functional index, as well as symptoms including Raynaud's phenomenon, dyspnea, fatigue, dysphagia, arthralgias, and cutaneous ulcers. Renal function tests remained within normal range. A total of 296 monthly treatments were administered without significant toxicity. CONCLUSIONS: This study suggests that extended use of extracorporeal photochemotherapy in the management of early-onset, diffuse PSS is well tolerated and may provide an increasingly beneficial clinical outcome.

Cytolytic response to HIV in patients with HIV disease treated with extracorporeal photochemotherapy: preliminary study.

Extracorporeal photochemotherapy (photopheresis), an immunomodulatory therapy that targets circulating T helper lymphocytes, has been applied to the management of human immunodeficiency virus (HIV) disease. Any therapy that exerts its actions on CD4+ T cells has the potential of exacerbating HIV infection. Therefore, it was necessary to observe immune function during treatment. Because cytotoxic T lymphocytes (CTL) and natural-killer cells are thought to play an important role in the response against HIV infection, we examined the effect of photopheresis on HIV cytolytic activity. The study group consisted of seven patients with late-stage HIV disease who had not received any previous treatment for HIV infection. Patients were treated exclusively with photopheresis on two consecutive days each month for 14-32 months (average, 25 months). Peripheral lymphocytes, collected at various points during treatment, were used as effectors in a 51Cr release assay. Epstein-Barr virus (EBV)-transformed autologous B cell lines transfected with recombinant vaccinia vectors that expressed the HIV env (gp120, gp41) and gag (p24) proteins were used as target cells. All seven patients demonstrated relatively constant levels of cytolysis (>10% above controls) during treatment in the context of stable CD4+ T cell counts and a stable clinical status. These results suggest that extracorporeal photochemotherapy did not impair the cytolytic response to HIV infection and may have enhanced it in some patients.